Capreomycin

Structural formula
	Structures of capreomycin IA (top) and capreomycin IB (bottom)
General
Non-proprietary name	Capreomycin
Molecular formula	C 25 H 44 N 14 O 8
Brief description	colorless solid
External identifiers / databases
PubChem	135483770
DrugBank	DB00314
Wikidata	Q415909
Drug information
ATC code	J04 AB30
Drug class	Antibiotics
Mechanism of action	Protein synthesis inhibitor
properties
Molar mass	668.71 g · mol -1
solubility	soluble in water, insoluble in organic solvents
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302-312-332-360
	P: 201-280-308 + 313
Toxicological data	250 mg kg −1 ( LD 50 , mouse , iv )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Capreomycin (trade name Capastat ; first manufacturer Eli Lilly ) is a drug from the group of polypeptide antibiotics , which is used as a second-line agent in the treatment of multi-drug-resistant tuberculosis .

Clinical information

Application areas (indications)

Capreomycin is used in combination with other antituberculotics to treat pulmonary tuberculosis when primary treatment with isoniazid , rifampicin, and ethambutol has not been effective and when combination therapy with 4-aminosalicylic acid (PAS) and streptomycin also fails. The sensitivity of the pathogen Mycobacterium tuberculosis to capreomycin should be determined in each patient.

Adverse effects (side effects)

Damage to the kidneys and the inner ear ( ototoxicity ) are very common side effects . Accordingly, kidney and hearing function should be monitored before and during treatment. Liver damage and changes in the blood count also occur. Hypersensitivity reactions are rare.

Pharmacological properties

Mechanism of action (pharmacodynamics)

Capreomycin works by inhibiting protein biosynthesis in the bacterial cells by binding to both the 16S and the 23S rRNA , an unusual mechanism of action affecting both subunits of the ribosome , which is otherwise only described in the structurally related tuberculostatic viomycin , which was first isolated in 1949 has been. Mycobacteria that are resistant to capreomycin have an inactive tlyA gene; this gene codes for a methyltransferase that modifies both the 16S and the 23S rRNA at the binding site for capreomycin, making the ribosomes susceptible to inhibition by the antibiotic. Since only a few types of bacteria have a tlyA gene, the effect of capreomycin is essentially limited to mycobacteria.

Absorption and distribution in the body (pharmacokinetics)

The absorption of the drug after oral administration is very low, so the administration is always intramuscular or intravenous . With normal kidney function, around 50% of the drug is excreted unchanged in the urine within 12 hours.

Other Information

Chemical and pharmaceutical information

Capreomycin is a cyclic peptide that is obtained from Streptomycetes , bacteria of the species Streptomyces capreolus . The substance used in pharmaceuticals is a complex of four antimicrobially active components: Capreomycin IA, IB, IIA and IIB. The antibiotic is sometimes counted among the aminoglycosides because of its similar effect on bacterial translation , although there is no structural relationship.

History

The antibiotic was developed by Eli Lilly in the 1960s. it was approved in the USA on June 2, 1971. No drugs with this active ingredient are approved in Germany.

Individual evidence

↑ ^a ^b entry on capreomycin. In: Römpp Online . Georg Thieme Verlag, accessed on November 11, 2014.
↑ ^a ^b Datasheet Capreomycin sulfate from Streptomyces capreolus from Sigma-Aldrich , accessed on May 23, 2017 ( PDF ).
↑ Entry on capreomycin in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ ^a ^b ^c FDA label Capastat Sulfate (PDF, English; 77 kB).
↑ Karl Wurm, AM Walter: Infectious Diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition, ibid. 1961, pp. 9–223, here: p. 55.
↑ ^a ^b ^c Johansen SK, Maus CE, Plikaytis BB, Douthwaite S. Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2'-O-methylations in 16S and 23S rRNAs. In: Mol Cell. 2006 Jul 21; 23 (2): 173-82. PMID 16857584

[roempp-1] try on capreomycin. In: Römpp Online . Georg Thieme Verlag, accessed on November 11, 2014.

[Sigma-2] Datasheet Capreomycin sulfate from Streptomyces capreolus from Sigma-Aldrich , accessed on May 23, 2017 ( PDF ).

[ChemIDplus-3] Entry on capreomycin in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[FDA-4] FDA label Capastat Sulfate (PDF, English; 77 kB).

[5] Karl Wurm, AM Walter: Infectious Diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition, ibid. 1961, pp. 9–223, here: p. 55.

[Mol_Cell-6] Johansen SK, Maus CE, Plikaytis BB, Douthwaite S. Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2'-O-methylations in 16S and 23S rRNAs. In: Mol Cell. 2006 Jul 21; 23 (2): 173-82. PMID 16857584